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PubMed1987

Changes in erythromycin pharmacokinetics induced by renal failure.

As erythromycin ototoxicity appears to be favored by renal insufficiency, its pharmacokinetics were assessed in chronic uremic patients treated by maintenance hemodialysis in comparison with normal subjects. Two groups of 8 patients each were studied, the first one on an interdialytic day, the second immediately after the end of an hemodialysis session. All subjects ingested a single dose of 1 gram of erythromycin ethylsuccinate. Times of peak serum concentration and biological half-lifes were similar in patients and in controls. Maximum serum concentrations and areas under the serum concentration time-curve were higher in patients than in controls whereas apparent oral clearances were lower in the former. The differences between the two groups of patients were not significant. These pharmacokinetic changes are suggestive of an enhanced bioavailability of erythromycin in chronic renal failure which might predispose uremics to the ototoxicity of the drug.

Adult↗
PubMed1976

Concentrations of erythromycin in serum and tonsil: comparison of the estolate and ethyl succinate suspensions.

Concentrations of erythromycin were measured in serum and tonsil from children who had received either the estolate or ethyl succinate suspension before surgery. The in vitro assay measured total erythromycin activity against a group A beta hemolytic streptococcus. Levels of erythromycin in serum and tonsil after single and multiple doses of the estolate were significantly higher than those after administration of the ethyl succinate. The therapeutic implications of these findings are unknown.

Biological Availability↗
PubMed1991

Ototoxic reaction to erythromycin.

We report a case of bilateral hearing loss in a patient treated with intravenous erythromycin lactobionate. The ototoxic reaction occurred despite the patient's having normal renal and hepatic function and the fact that serum erythromycin levels were within the predicted normal range. In addition to hearing loss, a marked labyrinthic hyporreflexia was also observed. Hearing loss improved after the treatment was discontinued, but labyrinthic abnormalities persisted suggesting that erythromycin had caused a permanent vestibular damage.

Erythromycin↗
PubMed1979

Sensitivity of group A streptococci to antibiotics. Prevalence of resistance to erythromycin in Japan.

More than 60% of all strains of group A streptococci isolated during the period from 1974 to 1975 from children with streptococcal infections in Hokkaido district, Japan, were highly resistant to erythromycin. These strains were found to be multiply resistant to lincomycin hydrochloride monohydrate, chloramphenicol, and tetracycline, and were exclusively type 12 by T-protein typing. The clinical symptoms produced by these organisms were rather mild, responded to penicillin well, and were rarely complicated with glomerulonephritis. The high prevalence of resistant group A streptococci was nationwide, which may have been related to recent excessive use of erythromycin and other macrolide antibiotics. Erythromycin can no longer be considered the drug of choice in the management of streptococcal infections in Japan. This suggests that a periodic surveillance of antibiotic sensitivity of streptococcal isolates may be necessary in other countries in which macrolide antibiotics are frequently prescribed.

Anti-Bacterial Agents↗
PubMed1982

Oral v topical erythromycin therapies for chlamydial conjunctivitis.

Results of oral and topical erythromycin therapy in 41 infants under 4 months of age with chlamydial conjunctivitis were evaluated in randomized clinical trial. After three weeks of treatment, relapse or reinfection of the eye occurred in four of 19 patients (21%) in the topical therapy group and in three of 22 patients (13.6%) in the oral therapy group (p less than .69). In the topical therapy group, chlamydiae were isolated from nasopharyngeal cultures of eight patients (42%) during or after therapy. Chlamydiae were eradicated from the nasopharynx of the six colonized patients treated with oral erythromycin. All relapses responded to a course of oral erythromycin therapy. We conclude that both modes of therapy are comparable for treatment of chlamydial conjunctivitis, but that oral therapy has the advantage of eradicating nasopharyngeal colonization.

Administration, Oral↗
PubMed1990

Impetigo. Current etiology and comparison of penicillin, erythromycin, and cephalexin therapies.

We attempted to determine the causative bacterial pathogens of impetigo in children in our area, to compare the effectiveness of three frequently used oral antimicrobial treatment regimens, and to correlate the antimicrobial sensitivity of the bacterial isolates with clinical responses to treatment. Seventy-three children with impetigo were randomly assigned to receive penicillin V potassium or cephalexin monohydrate, both administered in dosages of 40 to 50 mg/kg per day, or erythromycin estolate administered in a dosage of 30 to 40 mg/kg per day. All drugs were given in three divided doses for 10 days. Treatment failure was defined as persistence of lesions 8 to 10 days after initiation of drug therapy as determined by examiners blinded to the treatment therapies. Forty-five (62%) cultures showed Staphylococcus aureus only, 14 (19%) showed S aureus and group A beta-hemolytic streptococci, six (8%) showed group A beta-hemolytic streptococci only, and eight (11%) showed no growth or other organisms. Treatment failure occurred in six (24%) of 25 patients treated with penicillin V, one (4%) of 25 patients treated with erythromycin estolate, and no patients treated with cephalexin. We conclude that S aureus is the most common cause of impetigo in children in our study population, that cephalexin is the most effective treatment, that erythromycin estolate is nearly equally effective and may be preferred on a cost-effectiveness basis, and that penicillin V is inadequate for treatment of this infection.

Adolescent↗
PubMed1992

Prevention of secondary transmission of pertussis in households with early use of erythromycin.

To examine the effectiveness of erythromycin therapy and prophylaxis for pertussis, 17 households with one secondary case or more were compared with 20 households without secondary cases following a community-wide pertussis outbreak in Maricopa County, Arizona, in 1988. There were no significant differences between the two household groups in age distribution of members, size, crowding, race, proportion of children aged 7 months to 18 years with three or more diphtheria and tetanus toxoids and pertussis vaccine doses, or in the age distribution, vaccination status, or medical care of patients with primary cases. However, median intervals from onset of illness in primary cases to initiation of erythromycin therapy (for cases) and prophylaxis (for contacts) were 11 and 16 days, respectively, in households without secondary spread, vs 21 and 22 days, respectively, in households with secondary spread. These results provide additional evidence that erythromycin is effective in the medical management of pertussis and should be initiated promptly to minimize secondary spread.

Adolescent↗
PubMed2000

Separation and determination of the macrolide antibiotics (erythromycin, spiramycin and oleandomycin) by capillary electrophoresis coupled with fast reductive voltammetric detection.

Separation and determination of erythromycin, spiramycin and oleandomycin by capillary zone electrophoresis coupled with fast reductive voltammetric detection using an Hg-film electrode was investigated in a simple aqueous phosphate buffer system. The influence of pH, concentration of phosphate, applied voltage, capillary length and dimension on the separation was examined and optimized. The entire separation of erythromycin, spiramycin, and oleandomycin was achieved in a 0.2 mol/L phosphate buffer system without organic modifiers. The electrochemical detection parameters, such as electrode material, applied waveform, scan rate, preconcentration potentials and preconcentration times, were investigated and discussed. This approach provides high separation efficiency and high sensitivity for all compounds, with detection limits (3 x peak-to-peak baseline noise) of 7.5 x 10(-8) mol/L for spiramycin, and 3 x 10(-7) mol/ L for erythromycin and oleandomycin. The calibration plot of peak areas for each separated peak vs. concentration of analyte was found to be linear over three orders of magnitude.

Anti-Bacterial Agents↗
PubMed1990

Aggravation of myasthenia gravis by erythromycin.

Erythromycin is not currently recognized as causing clinical aggravation of myasthenia gravis. We report the case of a patient who experienced exacerbations of myasthenia gravis subsequent to each of several doses of intravenous erythromycin. We suggest that erythromycin can cause clinical worsening in patients with disease of the neuromuscular junction.

Adult↗
PubMedDate not supplied

Time-dependent inhibition of theophylline elimination by erythromycin stearate.

The effect of erythromycin stearate at a dose of 1 g daily on theophylline disposition was studied in six healthy adult males. The mean value of 5.46 h for the theophylline half-life after 48 h pretreatment with erythromycin stearate was not significantly different from the control value of 5.24 h. The half-life value of 8.48 h after a 1-week course of the antibiotic, however, represented a significant increase (p less than 0.005). Theophylline disposition 1 week after the last dose of the antibiotic was not significantly different from the control. It is suggested that therapeutic doses of erythromycin stearate for a week or more could impair the disposition of concurrently administered theophylline. The impairment however, is reversible, being absent a week after the last antibiotic dose.

Adult↗
PubMed1992

Effect of dehydration on the disposition kinetics of erythromycin in rabbits.

The effect of water deprivation on the physiologic, biochemical, and disposition parameters of erythromycin was investigated in rabbits. The packed cell volume, plasma glucose, and total lipid concentration increased significantly in dehydration. The pharmacokinetic parameters of erythromycin after intravenous administration also changed, suggesting a need for monitoring toxicity of erythromycin in the water-deprived population.

Animals↗
PubMed2006

Determination of erythromycin A in rat plasma and urine by high-performance liquid chromatography with chemiluminescence detection using Tris(2,2'-bipyridine)ruthenium(II).

A simple and sensitive method was developed for the determination of erythromycin A (EA), decladinosyl erythromycin A (dClEA) and erythromycin B (EB) in rat plasma and urine by high-performance liquid chromatography with electrogenerated chemiluminescence detection using Tris(2,2'-bipyridine)ruthenium(II). The recovery rates of EA, dClEA and EB were 97, 94 and 85% from rat plasma and 89, 83 and 93% from rat urine, respectively. The calibration curves were linear over the concentration ranges 0.05-5 microg/mL for plasma and 0.5-50 microg/mL for urine. The precision and accuracy for all analytes in rat plasma were < or =9.0 and -6.3-7.2%, and those in urine were < or =9.4% and -6.1-7.6%, respectively. This method proved to be a powerful tool for determination of EA, dClEA and EB concentrations in samples from rats.

2,2'-Dipyridyl↗
PubMed2004

Identification of a phosphopantetheinyl transferase for erythromycin biosynthesis in Saccharopolyspora erythraea.

Phosphopantetheinyl transferases (PPTases) catalyze the essential post-translational activation of carrier proteins (CPs) from fatty acid synthases (FASs) (primary metabolism), polyketide synthases (PKSs), and non-ribosomal polypeptide synthetases (NRPSs) (secondary metabolism). Bacteria typically harbor one PPTase specific for CPs of primary metabolism ("ACPS-type" PPTases) and at least one capable of modifying carrier proteins involved in secondary metabolism ("Sfp-type" PPTases). In order to identify the PPTase(s) associated with erythromycin biosynthesis in Saccharopolyspora erythraea, we have used the genome sequence of this organism to identify, clone, and express (in Escherichia coli) three candidate PPTases: an ACPS-type PPTase (S. erythraea ACPS) and two Sfp-type PPTases (a discrete enzyme (SePptII) and another that is integrated into a modular PKS subunit (SePptI)). In vitro analysis of these recombinant PPTases, with an acyl carrier protein-thioesterase (ACP-TE) didomain from the erythromycin PKS as substrate, revealed that only SePptII is active in phosphopantetheinyl transfer with this substrate. SePptII was also shown to provide complete modification of ACP-TE and of an entire multienzyme subunit from the erythromycin PKS in E. coli. The efficiency of the SePptII in phosphopantetheinyl transfer in E. coli makes it an attractive alternative to other Sfp-type PPTases for co-expression experiments with PKS proteins.

Acyl Carrier Protein↗
PubMed1985

Determination of erythromycin in serum and urine by high-performance liquid chromatography with ultraviolet detection.

A high-performance liquid chromatographic analysis of erythromycin in human serum and urine with UV detection at 200 nm is presented. The method involves a solid-phase extraction procedure followed by a simple phase separation step and chromatography on a reversed-phase column. The method has sensitivity limits of 0.25 and 1.0 micrograms/mL in serum and urine, respectively, and is sufficiently sensitive to monitor concentrations of erythromycin in human serum and urine after the administration of a single 500-mg erythromycin stearate tablet.

Chromatography, High Pressure Liquid↗
PubMed1997

Detection of erythromycin resistant methylase gene by the polymerase chain reaction.

A polymerase chain reaction (PCR) protocol was developed that could specifically amplify a 520-bp region of the erythromycin resistant methylase (ermC) gene sequence. The identity of the PCR-amplified 520-bp DNA was confirmed by HinCII endonuclease restriction digestion, which produced the predicted 440-bp and 80-bp DNA fragments. A 20-mer (alpha-32P) oligonucleotide probe specifically hybridized with these amplified products confirming the specificity and reliability of this diagnostic assay. The assay could detect the ermC gene in bacterial suspensions containing as few as 10(3) cells ml-1. The assay was used to detect the presence of the ermC gene in several Gram-positive bacterial strains identified as Streptococcus sp., Staphylococcus sp., Micrococcus sp., Lactobacillus sp. and Enterococcus sp., isolated from water samples maintained in experimental animal cages and clinical sources. Only bacteria identified as Staphylococcus sp. were resistant to the antibiotic. Although 17 strains of Staphylococcus sp. isolated from clinical samples were resistant to erythromycin, only seven of these isolates tested positive for the presence of the ermC gene. Of these strains, five were identified as coagulase-positive S. aureus and the rest were identified as coagulase-negative S. epidermidis. The erythromycin resistance in all seven ermC positive isolates was constitutive. The entire diagnostic assay, including template preparation, amplification and electrophoresis can be completed within 6 h.

Blotting, Southern↗
PubMed1999

Simultaneous detection of erythromycin-resistant methylase genes ermA and ermC from Staphylococcus spp. by multiplex-PCR.

A comparative analysis of the two most dominant erythromycin-resistance determinant genes in Staphylococcus sppnamely, the ermA and ermC genes, was carried out. Sixty erythromycin-resistant strains of Staphylococcus spp. were tested, of which 24 were avian and 36 were clinical isolates. Our results indicated the prevalence of ermA over the ermC gene as opposed to the widely held opinion of the ermC gene being the most dominant resistance determinant gene. A multiplex-PCR assay was developed to detect the presence of ermA and ermC genes. Two pairs of primers, specific for the detection of ermA and ermC genes, were used in a multiplex-polymerase chain reaction (PCR) assay to yield amplified DNA products of 610 and 520 bp, respectively. Their digestion with restriction enzyme FokI that yielded a 477 bp and a 132 bp digestion product for ermA and a 333 bp and a 187 bp digestion product for ermC confirmed the authenticity of PCR products. The method could be used to amplify the ermA and ermC genes with as little as 5 pg of template DNA. The use of excess primers or the template DNA resulted in gene-specific amplification and no non-specific amplification was observed by changing the primer to primer or template to primer ratios. Furthermore, no amplification from erythromycin-sensitive S. aureus strain was observed. Using this assay, the poultry strains were found to contain either ermA alone (50%) or a combination of ermA (100%) and ermC (50%) both. The clinical strains contained either ermA (94.5%) or ermC (5.5%) but never both. The gene-specific internal probes were also used to verify the above findings and a high degree of correlation between the multiplex PCR and Southern hybridization data was observed.

Animals↗
PubMed1995

The Corynebacterium xerosis composite transposon Tn5432 consists of two identical insertion sequences, designated IS1249, flanking the erythromycin resistance gene ermCX.

Analysis of the 50-kb R-plasmid pTP10 from the clinical isolate Corynebacterium xerosis M82B revealed that the erythromycin resistance gene, ermCX, is located on a 4524-bp composite transposable element, Tn5432. The ends of Tn5432 are identical, direct repeats of an insertion sequence, designated IS1249, encoding a putative transposase of the IS256 family. IS1249 consists of 1385 bp with 45/42 imperfect terminal inverted repeats. The nucleotide sequence of the 1754-bp Tn5432 central region is 99% identical to the previously sequenced erythromycin resistance region of the Corynebacterium diphtheriae plasmid pNG2. It encodes the erythromycin resistance gene, ermCX, and an ORF homologous to the amino-terminal end of the transposase of IS31831 from Corynebacterium glutamicum. Transposons with regions flanking the insertion sites were recovered from the C. glutamicum chromosome by a plasmid rescue technique. Insertion of Tn5432 created 8-bp target site duplications. A Tn5432-induced isoleucine/valine-auxotrophic mutant was found to carry the transposon in the 5' region of the ilvBNC cluster; in pTP10 the transposon is inserted in a region similar to replication and partitioning functions of the Enterococcus faecalis plasmid pAD1 and the Agrobacterium tumefaciens plasmid pTAR.

Amino Acid Sequence↗
PubMed1997

Isolation and characterization of a plasmid from Lactobacillus fermentum conferring erythromycin resistance.

Lactobacillus fermentum is a lactic acid bacterial species commonly found in the digestive tracts of pigs and rodents and also present in man. We characterized a 5.7-kb plasmid, pLEM3, conferring erythromycin resistance, which was isolated from a porcine strain of L. fermentum. Plasmid pLEM3 established efficiently in L. fermentum, conferred high-level erythromycin resistance (MIC > 1 mg/ml), and was segregationally stable. A deletion derivative of pLEM3, called pLEM5, was constructed and found to be as genetically stable as the parent. A multiple cloning site was inserted into pLEM5, generating plasmid pLEM7. Nucleotide sequence determination of pLEM5 revealed similarities with known genes. The replicon itself is a member of the pC194 family of rolling circle plasmids. The region responsible for erythromycin resistance was 98.2% identical to the erm gene of conjugative transposon Tn1545.

Animals↗